1. Field of the Invention
The present invention is directed to pyrithione biocides, and more particularly to a biocidal composition displaying an enhanced biocidal effect, comprising an antimicrobially effective combination of pyrithione, pyrithione salt, or pyrithione adduct, and metal ion such as a zinc or copper or silver source such as copper and/or zinc and/or silver metal, oxide, hydroxide, or salt thereof.
2. Brief Description of the Related Art
Polyvalent metal salts of pyrithione (also known as 1-hydroxy-2-pyridinethione; 2-pyridinethiol-1-oxide; 2-pyridinethione; 2-mercaptopyridine-N-oxide; pyridinethione; and pyridinethione-N-oxide) are known to be effective biocidal agents, and are widely used as fungicides and bacteriocides in paints and metalworking fluids. Pyrithiones are also used as fungicides and bacteriocides in personal care products such as anti-dandruff shampoos. The polyvalent metal salts of pyrithione are only sparingly soluble in water and include magnesium pyrithione, barium pyrithione, bismuth pyrithione, strontium pyrithione, copper pyrithione, zinc pyrithione, cadmium pyrithione, and zirconium pyrithione. The most widely used divalent pyrithione salts are zinc pyrithione and copper pyrithione.
Zinc and copper pyrithione are useful as antimicrobial agents active against gram-positive and negative bacteria, fungi, and yeasts. Zinc pyrithione is used as an antidandruff component in shampoos, while technical suspensions of zinc pyrithione and/or copper pyrithione are used as preservatives in paints and polymers. Synthesis of polyvalent pyrithione salts are described in U.S. Pat. No. 2,809,971 to Berstein et al. Other patents disclosing similar compounds and processes for making them include U.S. Pat. Nos. 2,786,847; 3,589,999; 3,590,035; 3,773,770.
While pyrithione biocides have proven useful for a wide range of applications as outlined above, the utility of these compounds is limited to the control of select species and strains of fungi and bacteria. Further, while higher concentrations of pyrithione or its salts have been observed to control the growth of a wider range of organisms, the useful amount of pyrithione or its salts that can be added to a commercial product is limited by efficacy and economic considerations, and, to a lesser extent, environmental and toxicological concerns.
Copper compounds, such as copper sulfate and cuprous oxide, have been used widely as fungicides, antifoulants, and algaecides in a large range of applications including paints, swimming pool water, and wood products such as structural members for buildings or boats. Similarly, inorganic salts of zinc such as zinc chloride zinc sulfate and zinc oxide, have been employed as bacteriostatic and/or fungistatic compounds in a large variety of products including paints, coatings, and antiseptics. However, while copper salts and zinc salts are less toxic than pyrithione or its salts, these compounds do not possess the high biocidal efficacy that is desired in many commercial applications.
Certain combinations of pyrithione and zinc are known in the art. Illustratively, U.S. Pat. Nos. 5,854,266 and 5,883,154 disclose an aqueous antimicrobial composition protected against discoloration attributable to the presence of ferric ion or cupric ion therein, wherein the composition comprises pyrithione and a discoloration-inhibiting amount (between 0.001% to 10%) of a zinc compound selected from the group consisting of zinc salts of organic acids, zinc salts of inorganic acids, zinc hydroxide, zinc oxide, and combinations thereof. In another illustration, U.S. Pat. No. 4,161,526 discloses a white to cream yellow pyrithione salt or dipyrithione for application to skin or hair containing 0.01% to 1% of the zinc salt of an organic or inorganic acid, zinc hydroxide, zinc oxide, or combinations thereof. However, this patent does not describe any advantageous effect between pyrithione and the zinc salt.
While bacteria and fungi have presented microbial contamination problems for many years, biofilms have recently been appreciated as a significant new source of microbial contamination. Biofilms are generally characterized as aggregates of cells adhered to one another or to surfaces by an extracellular layer of slime. Biofilms are commonly found as contaminants in metalworking fluids because these fluids contain good carbon sources for growth of the organisms that are found in biofilms. However, high concentrations of biofilms in metalworking fluid result in rapid deterioration of the fluid, and can cause equipment problems and failure.
The growth of biofilms on surfaces can also enhance the rates of corrosion of metal surfaces and degradation of paints, surface coatings and the construction materials underlying these coatings. On ship hulls, the presence of biofilms can lead to increased drag and may encourage colonization by larger invertebrate biofouling organisms. Biofilms are often responsible for both internal and cutaneous infections. The increased resistance of biofilms to antimicrobial treatments often make biofilm-related infections more difficult to treat. Medical devices, such as cardiac implants and catheters, and medical instruments, such as dialysis machines and dental waterlines also become contaminated by biofilms and can spread infection.
While previous efforts have been made to control the growth and proliferation of biofilms, these efforts have met with only limited success. Research has indicated that biofilm cells are much more resistant to disinfection than free-living cells, due in large part to the extracellular slime layer which acts as a protective coating. Moreover, strategies to control microbial contamination heretofore were typically developed in the laboratory against free-living organisms, and little or no attention was given towards determining the effectiveness of antimicrobial agents against biofilm. Unfortunately, the resistant biofilms are generally not affected by previously employed antimicrobials. If not removed or destroyed, biofilms can cause a multitude of problems in functioning fluid applications, such as corrosion, clogging, slime build up on surfaces, foul odors, fluid instability, machine down-time, and the like.
Additional representative patents and publications showing the state of the art in the microbial disinfection area are as follows:
U.S. Pat. No. 5,462,589 discloses a composition of made from a copper salt and sodium pyrithione, and chelates thereof. The mixture is applied sequentially, fixing the preservative in the wood.
U.S. Pat. No. 4,654,213 discloses an antimicrobial composition in which a water-soluble salt of zinc enhances the activity of the MgSO4 adduct of 2,2′-dithiopyridine-1,1′-dioxide (MDS).
U.S. Pat. No. 4,370,325 discloses a composition containing 2,2′-dithiopyridine-1,1′-dioxide or one of its metal salt adducts, including MgSO4 (MDS) and Zn salts, for treating eye and ear irritation and inflammation.
U.S. Pat. No. 4,235,873 discloses a deodorant composition containing 2,2′-dithiopyridine-1,1′-dioxide or one of its metal salt adducts, including MgSO4 (MDS) and Zn salts.
British Patent GB 2 230 190 A discloses a preservative composition containing an isothiazolone and the ZnCl2 adduct of 2,2′-dithiopyridine-1,1′-dioxide. However, this patent does not describe any advantageous effect between pyrithione and the zinc salt.
Japanese patent application 6-134227 discloses an antibacterial filter incorporating ZnO or ZnO and zinc pyrithione. However, this patent does not describe any advantageous effect between pyrithione and the zinc salt.
Japanese patent application 7-118103 discloses an antimicrobial composition for coating stainless steel washing machine drums to prevent fouling of inner surfaces wherein ZnO is used as a carrier in a ZPT thermoplastic resin coating. However, this patent does not describe any advantageous effect between pyrithione and the zinc salt.
Japanese patent application 06256689 discloses antifungal coatings composed of zeolites impregnated with heavy metals, preferably silver, and either a benzimidazole or a metal salt of 2-pyridiylthio-1-oxide, preferably, zinc.
ZnO may enhance the activities of hinokitiol, and certain antibiotics against artificial biofilms of S. aureus (Effects of Zinc Oxide on the Attachment of Staphylococcus aureus Strains, H. Akiyama, et al., J. Dermatol. Science 17: 67-74, 1998)
The presence of 0.2% metallic copper or 0.2% metallic zinc was found to decrease the biocidal activity sodium pyrithione in 12 different metalworking fluids (E. O. Bennet et al. (1982) Int. Biodeterioration Bull. 18[1]:7-12).
Accordingly, what is needed in the art is biocidal composition that offers the biocidal efficacy of pyrithione and its derivatives against free-living microorganisms and biofilms, that is highly efficacious and cost-effective, but without environmental and toxicological effects. The present invention is believed to be an answer to that need.